Background: The overall malignancy rate for the thyroid fine-needle aspiration (FNA) diagnosed as atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) ranges from 5-30%. It has been recommended to sub-classify AUS/FLUS diagnosis for better patient triage (repeat FNA vs. surgical excision). At our institution, all AUS/FLUS cases include a note regarding the cytomorphologic findings and suspicion for or against a neoplastic process. In this study, we present our experience with cases diagnosed as AUS/FLUS with sub-classifiers.Design: A search of our laboratory information system was performed to identify all in-house thyroid FNA cases diagnosed as AUS/FLUS from 2008-2011. The data was collected and characterized by patient demographic information, cytopathology diagnosis with sub-classifiers and follow up.Results: The case cohort included 348 cases diagnosed as AUS/FLUS in 87 males and 261 females. These were sub-classified into one of the following subcategories (SC): SC1 - favor benign, however, a follicular neoplasm (FN) could not be excluded due to increased cellularity; SC2 - specimens with focal nuclear overlapping and crowding; SC3 - scant specimens with focal nuclear overlapping and crowding; SC4 - specimens with focal nuclear overlapping and crowding in a background of lymphocytic thyroiditis; SC5 - few cells with features suspicious for papillary thyroid cancer (PTC), SC6 - specimens in which a FN cannot be excluded (with miscellaneous morphologic descriptors). Of the 348 cases, 13 (4%) were sub-classified as SC1, 127 (36%) as SC2, 128 (37%) as SC3, 52 (15%) as SC4, 17 (5%) as SC5 and 11 (3%) as SC6. Histologic follow-up was available in 139 (40%) cases; 45 (32%) cases were found to be malignant. The malignancy rate for each subcategory was: SC1 - 0%, SC2 - 36%, SC3 - 33%, SC4 - 22%, SC5 - 7% and SC6 - 2%.Conclusions: Sub-classifying AUS/FLUS diagnosis may prove to be helpful in the management of patients with thyroid nodules.Category: Quality Assurance